I have the pleasure of co-authoring this presentation with
Drs. Gita Ramjee, Joanne Mantell and Landon Myer. Because of the crucial
importance of to-day’s meeting to the future of microbicide development, we
want to bring to the attention of our colleagues one new set of observations
just off the computer, not yet peer-reviewed (although read and approved
informally by severalcolleagues) and
not yet submitted for publication. The set of observations we want to share
with you concerns qualitative data, based on interviews and focus groups with
women who had contributed a major source of data for
the N9 study that we all know so well, in which the placebo (Replens) appeared
to have done more to protect users than the putative microbicide, N9.The women on the Ramjee-Mantell-Myer study
were interviewed some months after the termination of the trial, and after the
results had been communicated to them.

For our purposes to-day, this is the relevant message: many
women, although they understood that some of them were using a “placebo” and
that in any case, the gel under test had not been established as preventive,
still they liked using a gel; they felt it was cleansing, and that it probably
kept out what was harmful in the semen; and that so good did it feel that they
rejected the male condom in favor of the gel: they had of course been strongly
and repeatedly counseled against doing just that.But for our purposes to-day, these
observations give us the information for the first time that use of the gel (at
least among these sex-workers) encouraged them to disregard advice and
“emigrate” from use of the male condom.

This is very serious for the whole field. But we’re using
this information here for just two purposes: one is, once again, to argue
against the use of the “condom only” or, as the more recent phrase goes “no
gel” arm; the other is for a standard “placebo.”

These data demonstrate that emigration from the male condom
is not just a hypothetical possibility, but an observed phenomenon that can be
expected in future phase 3 trials. This could mean higher levels of condom use
in the open arm and different risks of HIV infection.

The idea of adding an open arm evidently emerged with our
puzzlement over the results of the N9 trial. Now that we have these post-trial
observations, it suggests to us that even if there had been a condoms only arm
with that trial, we would still have been puzzled. Because Ladysmith sex
workers would have emigrated from the male condom.

We are left to try and measure and adjust statistically for
such variations in condom use.The male
condom if correctly used, will protect, so that if
Replens is indeed inert, the condoms only arm should have given more
protection. If, then the condoms only arm had shown the most
protection, how would we have distinguished presumed emigration from the
possibility that Replens was harmful?No way to do that, save to rely on diaries and reports, from women on
gels and condoms, which we could never regard as trustworthy enough for a
definitive, multicenter trial like those.

If, on the other hand, Replens had proved superior to
condoms only, we would need to establish that, in a future trial, the condoms
only group also did not emigrate, or differentially increased their use. . In
fact, key to the interpretation of any open arm is the “soft” information we
obtain on continuing use of the condom across all groups. All this would become
even more complex, given the different range of condom use and expected
incidence of infection in each group. We would have to rely on highly
sophisticated estimates, based as we all would be aware, on the diaries and
reports.